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Infants’ head circumference larger with PCOS moms on metformin
Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.
Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.
The study was a post hoc analysis of data from the PregMet study, which was run from 2005 to 2009, and compared metformin to placebo, in combination with diet and lifestyle changes, for women with PCOS, said Dr. Hjorth-Hansen. The PregMet study tested the hypothesis that women with PCOS who received metformin from the first trimester until delivery had fewer pregnancy complications overall than women who did not.
Though women receiving placebo in the PregMet study had no more eclampsia, preterm delivery, or gestational diabetes than those who received metformin, the newborns who had in utero metformin exposure had significantly larger head circumference.
Dr. Hjorth-Hansen said that the study looked at in utero growth and anthropometric measurements at birth of infants born to women taking metformin, to determine whether metformin could affect fetal growth and newborn anthropometrics.
Ultrasound examination was used to measure crown-rump length, biparietal diameter (BPD), and mean abdominal diameter (MAD). At birth, head circumference (HC), length, and weight were measured.
Maternal characteristics were comparable between the metformin (131 patients) and placebo (127 patients) groups, said Dr. Hjorth-Hansen. Specifically, there were no significant differences between groups in terms of PCOS phenotype, blood glucose levels, and parity.
Infants born to women who took metformin had, on average, a larger BPD at 32 weeks gestation, compared with the infants whose mothers took placebo (86.1 mm versus 85.2 mm, P = .027). This larger head size was also seen at birth (mean HC, metformin, 35.6 cm; placebo, 35.0 cm; P = .007).
There were no significant differences between the groups in MAD or weight, either as assessed by ultrasound at 32 weeks gestation or as measured at birth.
Although the two groups did not differ in length at birth, the aggregate study population of infants born to women with PCOS was shorter than a large Swedish reference population.
When Dr. Hjorth-Hansen and her colleagues stratified the results by maternal body mass index (BMI), looking at babies born to women with BMIs below 25 kg/m2, compared with those with BMI of 25 kg/m2 and greater, they saw no differences in infant anthropometric measurements for women who had taken placebo.
However, when the investigators dichotomized maternal BMI for the metformin group, they found that infants born to the higher BMI group had a larger head size (P = .022), and were heavier (P = .002) and longer (P = .003) than infants born to women with BMIs less than 25.
“Metformin resulted in a larger head size, traceable already in utero,” said Dr. Hjorth-Hansen. However, she said, there’s a “PCOS effect” that results in the offspring of women with the condition to have a shorter body, compared with offspring of women without PCOS.
Dr. Hjorth-Hansen reported no relevant disclosures.
koakes@frontlinemedcom.com
On Twitter @karioakes
Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.
Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.
The study was a post hoc analysis of data from the PregMet study, which was run from 2005 to 2009, and compared metformin to placebo, in combination with diet and lifestyle changes, for women with PCOS, said Dr. Hjorth-Hansen. The PregMet study tested the hypothesis that women with PCOS who received metformin from the first trimester until delivery had fewer pregnancy complications overall than women who did not.
Though women receiving placebo in the PregMet study had no more eclampsia, preterm delivery, or gestational diabetes than those who received metformin, the newborns who had in utero metformin exposure had significantly larger head circumference.
Dr. Hjorth-Hansen said that the study looked at in utero growth and anthropometric measurements at birth of infants born to women taking metformin, to determine whether metformin could affect fetal growth and newborn anthropometrics.
Ultrasound examination was used to measure crown-rump length, biparietal diameter (BPD), and mean abdominal diameter (MAD). At birth, head circumference (HC), length, and weight were measured.
Maternal characteristics were comparable between the metformin (131 patients) and placebo (127 patients) groups, said Dr. Hjorth-Hansen. Specifically, there were no significant differences between groups in terms of PCOS phenotype, blood glucose levels, and parity.
Infants born to women who took metformin had, on average, a larger BPD at 32 weeks gestation, compared with the infants whose mothers took placebo (86.1 mm versus 85.2 mm, P = .027). This larger head size was also seen at birth (mean HC, metformin, 35.6 cm; placebo, 35.0 cm; P = .007).
There were no significant differences between the groups in MAD or weight, either as assessed by ultrasound at 32 weeks gestation or as measured at birth.
Although the two groups did not differ in length at birth, the aggregate study population of infants born to women with PCOS was shorter than a large Swedish reference population.
When Dr. Hjorth-Hansen and her colleagues stratified the results by maternal body mass index (BMI), looking at babies born to women with BMIs below 25 kg/m2, compared with those with BMI of 25 kg/m2 and greater, they saw no differences in infant anthropometric measurements for women who had taken placebo.
However, when the investigators dichotomized maternal BMI for the metformin group, they found that infants born to the higher BMI group had a larger head size (P = .022), and were heavier (P = .002) and longer (P = .003) than infants born to women with BMIs less than 25.
“Metformin resulted in a larger head size, traceable already in utero,” said Dr. Hjorth-Hansen. However, she said, there’s a “PCOS effect” that results in the offspring of women with the condition to have a shorter body, compared with offspring of women without PCOS.
Dr. Hjorth-Hansen reported no relevant disclosures.
koakes@frontlinemedcom.com
On Twitter @karioakes
Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.
Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.
The study was a post hoc analysis of data from the PregMet study, which was run from 2005 to 2009, and compared metformin to placebo, in combination with diet and lifestyle changes, for women with PCOS, said Dr. Hjorth-Hansen. The PregMet study tested the hypothesis that women with PCOS who received metformin from the first trimester until delivery had fewer pregnancy complications overall than women who did not.
Though women receiving placebo in the PregMet study had no more eclampsia, preterm delivery, or gestational diabetes than those who received metformin, the newborns who had in utero metformin exposure had significantly larger head circumference.
Dr. Hjorth-Hansen said that the study looked at in utero growth and anthropometric measurements at birth of infants born to women taking metformin, to determine whether metformin could affect fetal growth and newborn anthropometrics.
Ultrasound examination was used to measure crown-rump length, biparietal diameter (BPD), and mean abdominal diameter (MAD). At birth, head circumference (HC), length, and weight were measured.
Maternal characteristics were comparable between the metformin (131 patients) and placebo (127 patients) groups, said Dr. Hjorth-Hansen. Specifically, there were no significant differences between groups in terms of PCOS phenotype, blood glucose levels, and parity.
Infants born to women who took metformin had, on average, a larger BPD at 32 weeks gestation, compared with the infants whose mothers took placebo (86.1 mm versus 85.2 mm, P = .027). This larger head size was also seen at birth (mean HC, metformin, 35.6 cm; placebo, 35.0 cm; P = .007).
There were no significant differences between the groups in MAD or weight, either as assessed by ultrasound at 32 weeks gestation or as measured at birth.
Although the two groups did not differ in length at birth, the aggregate study population of infants born to women with PCOS was shorter than a large Swedish reference population.
When Dr. Hjorth-Hansen and her colleagues stratified the results by maternal body mass index (BMI), looking at babies born to women with BMIs below 25 kg/m2, compared with those with BMI of 25 kg/m2 and greater, they saw no differences in infant anthropometric measurements for women who had taken placebo.
However, when the investigators dichotomized maternal BMI for the metformin group, they found that infants born to the higher BMI group had a larger head size (P = .022), and were heavier (P = .002) and longer (P = .003) than infants born to women with BMIs less than 25.
“Metformin resulted in a larger head size, traceable already in utero,” said Dr. Hjorth-Hansen. However, she said, there’s a “PCOS effect” that results in the offspring of women with the condition to have a shorter body, compared with offspring of women without PCOS.
Dr. Hjorth-Hansen reported no relevant disclosures.
koakes@frontlinemedcom.com
On Twitter @karioakes
FROM ENDO 2017
Key clinical point:
Major finding: Infants born to women with PCOS who took metformin during pregnancy had larger head circumferences at birth than those born to women with PCOS who took placebo (35.6 cm versus 35.0 cm, P = .007).
Data source: Retrospective analysis of data from 258 women in the PregMet study.
Disclosures: Dr. Hjorth-Hansen reported no relevant disclosures.
Most children with growth disorders benefit from growth hormone
ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.
Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.
The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.
All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.
“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”
The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.
Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.
The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.
At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.
At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.
Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.
Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.
Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.
The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.
Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.
Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.
The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.
All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.
“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”
The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.
Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.
The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.
At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.
At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.
Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.
Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.
Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.
The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.
Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.
Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.
The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.
All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.
“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”
The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.
Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.
The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.
At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.
At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.
Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.
Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.
Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.
The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.
Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT ENDO 2017
Key clinical point:
Major finding: Overall, 80% of the treated children reached normal adult height.
Data source: The prospective observational cohort study comprised 5,076 children.
Disclosures: Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.
Bioidentical hormone replacement fares well in phase III trial
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
Key clinical point:
Major finding: Four different dose combinations of 17 beta estradiol and progesterone improved hot flashes and menopause-related quality of life, compared with placebo (P less than .05 for all).
Data source: Multicenter randomized, double-blind, placebo-controlled study of 1,835 postmenopausal women with an intact uterus.
Disclosures: Dr. Lobo reported receiving research funding from TherapeuticsMD, which sponsored the study.
Osilodrostat maintained cortisol control in Cushing’s syndrome
ORLANDO – Osilodrostat, a drug that normalized cortisol in 89% of patients with Cushing’s syndrome who took it during a phase II study, continued to exert a sustained benefit during a 31-month extension phase.
In an intent-to-treat analysis, all of the 16 patients who entered the LINC-2 extension study responded well to the medication, with no lapse in cortisol control, Rosario Pivonello, MD, said at the annual meeting of the Endocrine Society.
Osilodrostat, made by Novartis, is an oral inhibitor of 11 beta–hydroxylase. The enzyme catalyzes the last step of cortisol synthesis in the adrenal cortex. The drug was granted orphan status in 2014 by the European Medicines Agency.
In the LINC-2 study, 19 patients took osilodrostat at an initial dose of either 4 mg/day or 10 mg/day, if baseline urinary-free cortisol exceeded three times the upper normal limit. The dose was escalated every 2 weeks to up to 60 mg/day, until cortisol levels were at or below the upper limit of normal. In this study, the main efficacy endpoint was normalization of cortisol, or at least a 50% decrease from baseline at weeks 10 and 22.
Overall response was 89%. Osilodrostat treatment reduced urinary-free cortisol in all patients, and 79% had normal cortisol levels at week 22. The most common adverse events were nausea, diarrhea, asthenia, and adrenal insufficiency. New or worsening hirsutism and/or acne were reported among four female patients, all of whom had increased testosterone levels.
The LINC-2 extension study enrolled 16 patients from the phase II cohort, all of whom had responded to the medication. They were allowed to continue on their existing effective dose through the 31-month period.
Dr. Pivonello presented response curves that tracked cortisol levels from treatment initiation in the LINC-2 study. The median baseline cortisol level was about 1,500 nmol per 24 hours. By the fourth week of treatment, this had normalized in all of the patients who entered the extension phase. The response curve showed continued, stable cortisol suppression throughout the entire 31-month period.
Four patients dropped out during the course of the study. Dr. Pivonello didn’t discuss the reasons for these dropouts. He did break down the results by response, imputing the missing data from these four patients. In this analysis, the majority (87.5%) were fully controlled, with urinary-free cortisol in the normal range. The remainder were partially controlled, experiencing at least a 50% decrease in cortisol from their baseline levels. These responses were stable, with no patient experiencing loss of control over the follow-up period.
The 12 remaining patients are still taking the medication, and they experienced other clinical improvements as well. Systolic blood pressure decreased by a mean of 2.2% (from 130 mm Hg to 127 mm Hg). Diastolic blood pressure also improved, by 6% (from 85 mm Hg to 80 mm Hg).
Fasting plasma glucose dropped from a mean of 89 mg/dL to 82 mg/dL. Weight decreased from a mean of 84 kg to 74 kg, with a corresponding decrease in body mass index, from 29.6 kg/m2 to 26.2 kg/m2.
Serum aldosterone decreased along with cortisol, dropping from a mean of 168 pmol/L to just 19 pmol/L. Adrenocorticotropic hormone increased, as did 11-deoxycortisol, 11-deoxycorticosterone, and testosterone.
Pituitary tumor size was measured in six patients. It increased in three and decreased in three. Dr. Pivonello didn’t discuss why this might have occurred.
The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. These moderated over time in both number and severity.
However, there were eight serious adverse events among three patients, including prolonged Q-T interval on electrocardiogram, food poisoning, gastroenteritis, headache, noncardiac chest pain, symptoms related to pituitary tumor (two patients), and uncontrolled Cushing’s syndrome.
Two patients experienced hypokalemia. Six experienced mild events related to hypocortisolism.
Novartis is pursuing the drug with two placebo-controlled phase III studies (LINC-3 and LINC-4), Dr. Pivonello said. An additional phase II study is being conducted in Japan.
Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
ORLANDO – Osilodrostat, a drug that normalized cortisol in 89% of patients with Cushing’s syndrome who took it during a phase II study, continued to exert a sustained benefit during a 31-month extension phase.
In an intent-to-treat analysis, all of the 16 patients who entered the LINC-2 extension study responded well to the medication, with no lapse in cortisol control, Rosario Pivonello, MD, said at the annual meeting of the Endocrine Society.
Osilodrostat, made by Novartis, is an oral inhibitor of 11 beta–hydroxylase. The enzyme catalyzes the last step of cortisol synthesis in the adrenal cortex. The drug was granted orphan status in 2014 by the European Medicines Agency.
In the LINC-2 study, 19 patients took osilodrostat at an initial dose of either 4 mg/day or 10 mg/day, if baseline urinary-free cortisol exceeded three times the upper normal limit. The dose was escalated every 2 weeks to up to 60 mg/day, until cortisol levels were at or below the upper limit of normal. In this study, the main efficacy endpoint was normalization of cortisol, or at least a 50% decrease from baseline at weeks 10 and 22.
Overall response was 89%. Osilodrostat treatment reduced urinary-free cortisol in all patients, and 79% had normal cortisol levels at week 22. The most common adverse events were nausea, diarrhea, asthenia, and adrenal insufficiency. New or worsening hirsutism and/or acne were reported among four female patients, all of whom had increased testosterone levels.
The LINC-2 extension study enrolled 16 patients from the phase II cohort, all of whom had responded to the medication. They were allowed to continue on their existing effective dose through the 31-month period.
Dr. Pivonello presented response curves that tracked cortisol levels from treatment initiation in the LINC-2 study. The median baseline cortisol level was about 1,500 nmol per 24 hours. By the fourth week of treatment, this had normalized in all of the patients who entered the extension phase. The response curve showed continued, stable cortisol suppression throughout the entire 31-month period.
Four patients dropped out during the course of the study. Dr. Pivonello didn’t discuss the reasons for these dropouts. He did break down the results by response, imputing the missing data from these four patients. In this analysis, the majority (87.5%) were fully controlled, with urinary-free cortisol in the normal range. The remainder were partially controlled, experiencing at least a 50% decrease in cortisol from their baseline levels. These responses were stable, with no patient experiencing loss of control over the follow-up period.
The 12 remaining patients are still taking the medication, and they experienced other clinical improvements as well. Systolic blood pressure decreased by a mean of 2.2% (from 130 mm Hg to 127 mm Hg). Diastolic blood pressure also improved, by 6% (from 85 mm Hg to 80 mm Hg).
Fasting plasma glucose dropped from a mean of 89 mg/dL to 82 mg/dL. Weight decreased from a mean of 84 kg to 74 kg, with a corresponding decrease in body mass index, from 29.6 kg/m2 to 26.2 kg/m2.
Serum aldosterone decreased along with cortisol, dropping from a mean of 168 pmol/L to just 19 pmol/L. Adrenocorticotropic hormone increased, as did 11-deoxycortisol, 11-deoxycorticosterone, and testosterone.
Pituitary tumor size was measured in six patients. It increased in three and decreased in three. Dr. Pivonello didn’t discuss why this might have occurred.
The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. These moderated over time in both number and severity.
However, there were eight serious adverse events among three patients, including prolonged Q-T interval on electrocardiogram, food poisoning, gastroenteritis, headache, noncardiac chest pain, symptoms related to pituitary tumor (two patients), and uncontrolled Cushing’s syndrome.
Two patients experienced hypokalemia. Six experienced mild events related to hypocortisolism.
Novartis is pursuing the drug with two placebo-controlled phase III studies (LINC-3 and LINC-4), Dr. Pivonello said. An additional phase II study is being conducted in Japan.
Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
ORLANDO – Osilodrostat, a drug that normalized cortisol in 89% of patients with Cushing’s syndrome who took it during a phase II study, continued to exert a sustained benefit during a 31-month extension phase.
In an intent-to-treat analysis, all of the 16 patients who entered the LINC-2 extension study responded well to the medication, with no lapse in cortisol control, Rosario Pivonello, MD, said at the annual meeting of the Endocrine Society.
Osilodrostat, made by Novartis, is an oral inhibitor of 11 beta–hydroxylase. The enzyme catalyzes the last step of cortisol synthesis in the adrenal cortex. The drug was granted orphan status in 2014 by the European Medicines Agency.
In the LINC-2 study, 19 patients took osilodrostat at an initial dose of either 4 mg/day or 10 mg/day, if baseline urinary-free cortisol exceeded three times the upper normal limit. The dose was escalated every 2 weeks to up to 60 mg/day, until cortisol levels were at or below the upper limit of normal. In this study, the main efficacy endpoint was normalization of cortisol, or at least a 50% decrease from baseline at weeks 10 and 22.
Overall response was 89%. Osilodrostat treatment reduced urinary-free cortisol in all patients, and 79% had normal cortisol levels at week 22. The most common adverse events were nausea, diarrhea, asthenia, and adrenal insufficiency. New or worsening hirsutism and/or acne were reported among four female patients, all of whom had increased testosterone levels.
The LINC-2 extension study enrolled 16 patients from the phase II cohort, all of whom had responded to the medication. They were allowed to continue on their existing effective dose through the 31-month period.
Dr. Pivonello presented response curves that tracked cortisol levels from treatment initiation in the LINC-2 study. The median baseline cortisol level was about 1,500 nmol per 24 hours. By the fourth week of treatment, this had normalized in all of the patients who entered the extension phase. The response curve showed continued, stable cortisol suppression throughout the entire 31-month period.
Four patients dropped out during the course of the study. Dr. Pivonello didn’t discuss the reasons for these dropouts. He did break down the results by response, imputing the missing data from these four patients. In this analysis, the majority (87.5%) were fully controlled, with urinary-free cortisol in the normal range. The remainder were partially controlled, experiencing at least a 50% decrease in cortisol from their baseline levels. These responses were stable, with no patient experiencing loss of control over the follow-up period.
The 12 remaining patients are still taking the medication, and they experienced other clinical improvements as well. Systolic blood pressure decreased by a mean of 2.2% (from 130 mm Hg to 127 mm Hg). Diastolic blood pressure also improved, by 6% (from 85 mm Hg to 80 mm Hg).
Fasting plasma glucose dropped from a mean of 89 mg/dL to 82 mg/dL. Weight decreased from a mean of 84 kg to 74 kg, with a corresponding decrease in body mass index, from 29.6 kg/m2 to 26.2 kg/m2.
Serum aldosterone decreased along with cortisol, dropping from a mean of 168 pmol/L to just 19 pmol/L. Adrenocorticotropic hormone increased, as did 11-deoxycortisol, 11-deoxycorticosterone, and testosterone.
Pituitary tumor size was measured in six patients. It increased in three and decreased in three. Dr. Pivonello didn’t discuss why this might have occurred.
The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. These moderated over time in both number and severity.
However, there were eight serious adverse events among three patients, including prolonged Q-T interval on electrocardiogram, food poisoning, gastroenteritis, headache, noncardiac chest pain, symptoms related to pituitary tumor (two patients), and uncontrolled Cushing’s syndrome.
Two patients experienced hypokalemia. Six experienced mild events related to hypocortisolism.
Novartis is pursuing the drug with two placebo-controlled phase III studies (LINC-3 and LINC-4), Dr. Pivonello said. An additional phase II study is being conducted in Japan.
Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT ENDO 2017
Key clinical point:
Major finding: Every patient in the study responded either fully (87.5%) or partially, with a decrease of at least 50% in cortisol from baseline (12.5%), with no loss of control.
Data source: The 31-month extension study comprised 16 patients who had responded well to the drug in a phase II trial.
Disclosures: Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.
Long-acting growth hormone moves forward based on positive phase II data
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
AT ENDO 2017
Key clinical point:
Major finding: In the 64-patient pediatric study, the molecule raised growth velocity and IGF-1 levels by several standard deviations. In the 48-patient adult study, it raised IGF-1 levels by up to 4 standard deviations.
Data source: A 64-patient pediatric dose-ranging study and a 48-patient adult study.
Disclosures: Versartis sponsored the studies. Dr. Yuen is on the company’s advisory board. Dr. Moore has received research support from the company.
Levothyroxine: No benefit for subclinical hypothyroidism in elderly
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
FROM ENDO 2017
Key clinical point: Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the therapy.
Major finding: The mean score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo after 1 year of treatment, and the mean score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Data source: An international randomized double-blind placebo-controlled clinical trial involving 737 older patients with subclinical hypothyroidism.
Disclosures: This study was supported by the European Union and several foundations. The levothyroxine and matching placebo were provided free of charge by Merck, which played no role in the design, analysis, or reporting of the study. Dr. Stott reported having no relevant financial disclosures; one of his associates reported ties to Bristol/Myers Squibb, Pfizer, and Bayer.
Temozolomide may help half of patients with aggressive pituitary tumors
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT ENDO 2017
Key clinical point:
Major finding: Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond.
Data source: The retrospective study comprised 43 patients treated in France.
Disclosures: Dr. Raverot had no financial disclosures.
Thyroid cancer incidence: It’s not all good news
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
AT ENDO 2017
Key clinical point:
Major finding: The incidence of thyroid cancer has dropped from 7 cases per 100,000 in 2000 to 2.2 cases per 100,000 in 2013 among whites. Among blacks it has increased from 5 cases to 7 cases per 100,000 over that time frame and in Hispanics from 7 cases to 12 cases per 100,000.
Data source: Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results data base.
Disclosures: The study received no external funding. Dr. Kotwal reported he had no relevant financial conflicts of interest.
Rotterdam Study: High T4 levels increased the risk for atherosclerotic events, death
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
AT ENDO 2017
Key clinical point: Major finding: The odds of an atherosclerotic event were 2.28 times higher in adults with elevated FT4 levels than those with high TSH, even when the high levels were still within the normal range.
Data source: Prospective study of 9,231 adults followed over 8.8 years.
Disclosures: Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
Milk interferes with levothyroxine absorption
ORLANDO – Consuming milk and levothyroxine at the same time reduced the absorption of the thyroid hormone replacement, according to Deborah Chon, MD, speaking at a press briefing at the annual meeting of the Endocrine Society.
This finding comes from a small study of 10 healthy adults with normal TSH concentration at baseline. The study participants had a mean age of 34 years and 6 were men.
The total serum T4 absorption over 6 hours, calculated as area under the curve, was significantly lower when participants took levothyroxine and milk concurrently, compared with taking it alone (67.26 vs. 73.48; P equals .02).
The best interval between taking levothyroxine and drinking milk has yet to be established, according to Dr. Chon, who is on the faculty of the University of California, Los Angeles. Findings from earlier research showed that use of elemental calcium supplements interfere with absorption of levothyroxine.
In 2014, levothyroxine became the most commonly prescribed drug in the United States, according to a survey by the IMS Institute for Healthcare Informatics, now QuintilesIMS. Patients who need to take it because of Hashimoto’s thyroiditis or after thyroidectomy are often unhappy with how they feel. Dose adjustments are common as endocrinologists struggle to improve patients’ quality of life. It may be that a simple strategy of not taking the thyroid replacement at the same time as milk might leave patients feeling better.
Dr. Chon reported having no relevant financial conflicts of interest.
This article was updated 4/10/17.
ORLANDO – Consuming milk and levothyroxine at the same time reduced the absorption of the thyroid hormone replacement, according to Deborah Chon, MD, speaking at a press briefing at the annual meeting of the Endocrine Society.
This finding comes from a small study of 10 healthy adults with normal TSH concentration at baseline. The study participants had a mean age of 34 years and 6 were men.
The total serum T4 absorption over 6 hours, calculated as area under the curve, was significantly lower when participants took levothyroxine and milk concurrently, compared with taking it alone (67.26 vs. 73.48; P equals .02).
The best interval between taking levothyroxine and drinking milk has yet to be established, according to Dr. Chon, who is on the faculty of the University of California, Los Angeles. Findings from earlier research showed that use of elemental calcium supplements interfere with absorption of levothyroxine.
In 2014, levothyroxine became the most commonly prescribed drug in the United States, according to a survey by the IMS Institute for Healthcare Informatics, now QuintilesIMS. Patients who need to take it because of Hashimoto’s thyroiditis or after thyroidectomy are often unhappy with how they feel. Dose adjustments are common as endocrinologists struggle to improve patients’ quality of life. It may be that a simple strategy of not taking the thyroid replacement at the same time as milk might leave patients feeling better.
Dr. Chon reported having no relevant financial conflicts of interest.
This article was updated 4/10/17.
ORLANDO – Consuming milk and levothyroxine at the same time reduced the absorption of the thyroid hormone replacement, according to Deborah Chon, MD, speaking at a press briefing at the annual meeting of the Endocrine Society.
This finding comes from a small study of 10 healthy adults with normal TSH concentration at baseline. The study participants had a mean age of 34 years and 6 were men.
The total serum T4 absorption over 6 hours, calculated as area under the curve, was significantly lower when participants took levothyroxine and milk concurrently, compared with taking it alone (67.26 vs. 73.48; P equals .02).
The best interval between taking levothyroxine and drinking milk has yet to be established, according to Dr. Chon, who is on the faculty of the University of California, Los Angeles. Findings from earlier research showed that use of elemental calcium supplements interfere with absorption of levothyroxine.
In 2014, levothyroxine became the most commonly prescribed drug in the United States, according to a survey by the IMS Institute for Healthcare Informatics, now QuintilesIMS. Patients who need to take it because of Hashimoto’s thyroiditis or after thyroidectomy are often unhappy with how they feel. Dose adjustments are common as endocrinologists struggle to improve patients’ quality of life. It may be that a simple strategy of not taking the thyroid replacement at the same time as milk might leave patients feeling better.
Dr. Chon reported having no relevant financial conflicts of interest.
This article was updated 4/10/17.
AT ENDO 2017
Key clinical point:
Major finding: Calculated as an area under the curve, simultaneous consumption of levothyroxine and milk reduced absorption of the supplement by a mean of 67.26 vs. 73.48 when taken without milk.
Data source: A pharmacokinetic study of 10 healthy subjects.
Disclosures: Dr. Chon reported having no relevant conflicts of interest.